The proposes study seeks to elucidate the genetic and environmental factors which contribute to the spontaneous thyroiditis of OS chickens and the iodide-induced thyroditis of CS chickens. Genetic differences between OS, CS and normal strains will be characterized by determination of thyroidal iodine contents and by comparison of the proliferative and functional responses of thyroid cells to TSH and iodide. Furthermore, transplantation and cell culture experiments will be performed to determine if thyroidal abnormalities play any role in the subsequent leukocyte infiltration and death of thyroid epithelial cells. The role of an hyperactive T cell system in causing thyroiditis in OS chickens will be studied by characterization of T cell subsets which are able to transfer disease and by the use of monoclonal antibodies to activated T cells, IL-2 and IL-2 receptors. The mechanisms by which dietary iodide induces autoimmune thyroiditis in CS chickens will be investigated by examining the relationship between TSH- independent thyroid function (already described in CS chickens), TSH plasma levels, dietary iodide, goitrogens and autoimmune thyroiditis. Chicken TSH will be purified and a TSH radioimmunometric assay will be developed for this purpose. Experiments will be performed to determine if acute thyroidal injury caused by serial administration of goitrogens and iodide results in chronic autoimmune thyroiditis in the genetically susceptible CS chicken. The role of iodide in OS thyroiditis will be investigated by assessing the effect of iodide depletion in ovo and after hatching. The specific role played by TG of high and low iodine contents in the disease will be studied by tolerance experiments. Since the spontaneous diseases in OS and CS chickens provide the best model for the human disease, the proposed studies should provide greater understanding of the etiology of human autoimmune thyroiditis.